Functionalized DNA nanostructures for templated biomineralization

矿化组织，如牙齿和骨骼，是通过由特殊细胞分泌的复杂蛋白质混合物引导的多步骤机制形成的。由于蛋白质溶液的成分不断变化，蛋白质模板分子变得高度组织化并最终转化为矿化组织的确切机制很难破译。对矿化组织形成的深入了解对于开发能够诱导牙齿和骨骼自我修复的生物材料至关重要。这项资助的假设是，将已知的诱导矿化的分子精确放置在表面上，将产生一种可能用作诱导和控制矿物晶体生长的贴片的材料。开发这种表面并以纳米精度组织材料的一种方法是使用合成DNA晶格；DNA纳米技术领域已经提出了大量的DNA纳米结构，这些结构已经被用来精确地组织其他分子。该基金的目标是：1)将合成DNA与已知的诱导矿化的分子偶联；2)将这些修饰过的DNA链整合到DNA晶格中；3)研究哪种结构和成分最能诱导形成与天然矿物性质相似的晶体。该项目的长期目标是通过放置能够诱导自然组织生长的功能化DNA贴片来再生受损的矿化组织。这些目标的成功完成将产生对生物矿化如何发生的更深入的理解。这一知识对于开发一种可用于自然牙齿和骨骼再生的材料至关重要。此外，该项目将为纳米医学领域的高素质人员提供培训，纳米医学是北美一个不断发展的领域。

Mineralized tissues, such as teeth and bone, form through a multi-step mechanism guided by a complex mixture of proteins secreted by specialized cells. The exact mechanism through which the proteins template molecules to become highly organized and eventually transform into a mineralized tissue is challenging to decipher because of the ever changing composition of the protein solution. A deeper understanding of mineralized tissue formation is essential for the development of a biomaterial capable of inducing self-healing in tooth and bone. The hypothesis of this grant is that the precise placement of molecules known to induce in mineralization onto a surface will yield a material that could potentially be used as a patch for inducing and controlling mineral crystal growth. One way to develop such a surface and to organize materials with nanometer precision is to use synthetic DNA lattices; the field of DNA Nanotechnology has put forth a plethora of DNA nanostructures that have been used to precisely organize other molecules. The objectives of this grant are: 1) to couple synthetic DNA to molecules known to induce mineralization; 2) to incorporate these modified DNA strands into DNA lattices; and 3) to study which configuration and composition best induces the formation of crystals with similar properties as naturally occurring minerals. The long-term goal of this project is to re-generate damaged mineralized tissues by placing functionalized DNA patches that can induce natural tissue growth. A successful completion of these objectives will yield a deeper understanding of how biomineralization occurs. This knowledge is essential for the development of a material that could be used for natural tooth and bone regeneration. In addition, this project will provide training for highly qualified personnel in nanomedicine, a growing field in North America.